反応式
[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([Cl:8])[C:3]=1[C:9]1[NH:10][C:11]2[CH:17]=[C:16]([C:18](Cl)=[O:19])[C:15]([F:21])=[C:14]([F:22])[C:12]=2[N:13]=1.[N:23]1[C:32]2[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=2)[CH:26]=[CH:25][C:24]=1[NH2:33].CCN(C(C)C)C(C)C>C1COCC1>[N:23]1[C:32]2[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=2)[CH:26]=[CH:25][C:24]=1[NH:33][C:18]([C:16]1[C:15]([F:21])=[C:14]([F:22])[C:12]2[N:13]=[C:9]([C:3]3[C:2]([Cl:1])=[CH:7][CH:6]=[CH:5][C:4]=3[Cl:8])[NH:10][C:11]=2[CH:17]=1)=[O:19]参加物
反応条件
- 温度
- 60 °C
実験手順
To a stirred suspension of 2-(2,6-dichlorophenyl)-6,7-difluoro-3H-benzoimidazole-5-carbonyl chloride (150 mg, 0.38 mmol) and quinolin-2-ylamine (55 mg, 0.38 mmol) in THF (10 mL) was added DIPEA (0.2 ml, 1.14 mmol) and the solution was heated at 60° C. for 4 days. The reaction was quenched with water and aqueous layer was extracted with EtOAc. The organic layer was washed with water, brine, dried with MgSO4, and filtered. The solvent was removed under reduced pressure and the residue was purified by flash chromatography using a gradient of heptane/EtOAc (4:1 to 100% EtOAc) to give 2-(2,6-dichlorophenyl)-6,7-difluoro-3H-benzoimidazole-5-carboxylic acid quinolin-2-ylamide as a white solid. 1H NMR (DMSO-d6, 400 MHz): δ 13.67 (s, 1H), 11.26 (s, 1H), 8.47 (d, 1H), 8.41 (d, 1H), 7.98 (d, 1H), 7.87 (d, 1H), 7.81 (d, 1H), 7.77 (m, 4H), 7.56 (m, 1H). MS (m/z) 469.1 (M+1); Retention time: 1.51 min (Method 10).
後処理
- customThe reaction was quenched with water and aqueous layer
- extractionwas extracted with EtOAc
- washThe organic layer was washed with water, brine
- dry with materialdried with MgSO4
- filtrationfiltered
- customThe solvent was removed under reduced pressure
- customthe residue was purified by flash chromatography
出典と根拠
- ORDレコード
- ord-513d97a00f5c474da0ed683d757e2c3e
- 出典データセット
- uspto-grants-2012_07
- 特許番号
- US08222248B2
関連ノート
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